Tetrazepam Allergy: a Case Series of Cutaneous Adverse Events

Acta Derm Venereol 2016; 96: 110–111

SHORT COMMUNICATION Tetrazepam Allergy: A Case Series of Cutaneous Adverse Events

Inga Huseynov, Mirja Wirtz and Nicolas Hunzelmann Department of Dermatology, University Hospital of Cologne, DTZ-West, Kerpener Straße 62, DE-50937 Köln, Germany. E-mail: [email protected] Accepted May 11, 2015; Epub ahead of print May 27, 2015

Tetrazepam has been widely used in clinical praxis in many Table I. Overview of patch- and prick-testing with tetrazepam and countries for over 50 years (1). As an agent belonging to diazepam in 8 patients with drug allergy to tetrazepam the class of benzodiazepines, it has an immediate sedative, Pat. Sex/age, Prick- Patch-test Patch-test muscle relaxing, anxiolytic and anticonvulsant effect. Ac- No. years Symptoms test (tetrazepam) (diazepam) cording to the German drug prescription report for 2012, 1 F/66 EME – Pos. at D2 Not done tetrazepam was the most commonly prescribed muscle 2 F/45 Exanthemaa – Pos. at D2 Not done relaxant after botulinum toxin (2). Common adverse 3 F/47 Exanthemaa – Pos. at D3 Not done 4 F/65 Exanthemaa – Pos. at D2 Not done reactions following systemic intake are of neurological 5 M/75 ME (see Fig. S21) – Pos. at D4 Not done and gastrointestinal nature, while cutaneous reactions to 6 M/48 Exanthemaa – Pos. at D3 Not done tetrazepam are very rare, with only a few cases reported 7 M/42 ME – Pos. at D2 Not done in the literature. It has nevertheless to be assumed that 8 F/49 Exanthema – Pos. at D2 Negative only a minority of cases is reported. The accumulation of aNot further specified exanthema. these adverse reactions in comparison with other muscle EME: erythema-multiforme-like exanthema; ME: maculopapular exanthema; relaxing drugs led the European Commission to suspend Pos.: positive; D2, D3, D4: days after test-application; –: negative. For further detailed information relating to each patient see Tables SI1 and SII1. marketing authorizations of tetrazepam-containing medi- cines across the European Union (EU) in 2013. As shown in Fig. S11, diazepam has great structural homology with To our knowledge, since 2002 16 cases of cutaneous tetrazepam, deviating only at R4 substitution (aromatic adverse effects due to tetrazepam have been published. ring (T) and cyclohexene ring (D)). Although the chemi- In most cases, patch-testing to tetrazepam was a sen- cal structure of these 2 muscle relaxants is very similar, sitive tool to detect hypersensitivity. Because there are with the exception of one report, all other reports failed no standardized testing protocols for tetrazepam, the to demonstrate cross-reactivity (3–5). patch-test concentrations ranged from 1% to 10% in A summary of skin reactions previously reported in pet. or aqua. In several patients skin testing was fol- the literature is shown in Table SI1, including (6) and (7). lowed by oral challenge testing, 5 out 7 re-challenges We retrospectively assessed patient charts in our allergy were positive. These results indicate that patch-testing clinic and identified 8 patients with tetrazepam allergy is a good tool to identify sensitization to tetrazepam. over a period of 10 years (2003–2013). Patch-testing Cross-reaction between tetrazepam and diazepam was had been performed as follows: the crushed tablets were demonstrated only in one case report (9). Most patients diluted with white petrolatum to 10% and applied to the tolerated diazepam despite its great structural similarity skin of the upper back for 48 h using Finn Chambers. to tetrazepam. The limited number of data in this regard Readings were made according to published guidelines has to be considered. Recently in healthcare workers, (8). The results of skin testing are summarized in Table I. e.g. via crushing of drug tablets to improve drug swal- A summary of the clinical data is available in Table SII1. lowing, airborne contact dermatitis and cross-reaction The patients in this case series are presented, in most between tetrazepam and benzodiazepines has been cases, as mild cutaneous reactions. Only one case pre- observed repeatedly (10, 11). sented as an erythema multiforme-like exanthema. In all Due to the withdrawal of tetrazepam, and only one patients skin reactions subsided without sequelae after case of documented cross-reactivity to diazepam, removal of the drug. Type IV sensitization to tetraze- physicians could take other benzodiazepine-derivates pam could be detected in all patients. Tests (prick and into therapeutic consideration. It remains to be seen patch) related to concomitant medication used at the whether skin testing and oral challenge test to other same time as tetrazepam showed no positive reactions, benzodiazepines derivates should be conducted prior suggesting that the observed skin reactions were very to applying these alternative treatment options. likely caused by tetrazepam. In addition, in one patient The authors declare no conflicts of interest. patch-testing of diazepam and in one patient oral challenge to lorazepam were negative. REFERENCES

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